Drugging IGF-1R in cancer: New insights and emerging opportunities

Genes and Diseases - Tập 10 - Trang 199-211 - 2023
Panpan Wang1, Victor CY. Mak1, Lydia WT. Cheung1
1School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

Tài liệu tham khảo

Weinstein, 2013, The cancer Genome atlas pan-cancer analysis project, Nat Genet, 45, 1113, 10.1038/ng.2764 Denduluri, 2015, Insulin-like growth factor (IGF) signaling in tumorigenesis and the development of cancer drug resistance, Genes Dis, 2, 13, 10.1016/j.gendis.2014.10.004 Lee, 2016, Inhibition of IGF1R signaling abrogates resistance to afatinib (BIBW2992) in EGFR T790M mutant lung cancer cells, Mol Carcinog, 55, 991, 10.1002/mc.22342 Browne, 2011, Inhibition of IGF1R activity enhances response to trastuzumab in HER-2-positive breast cancer cells, Ann Oncol, 22, 68, 10.1093/annonc/mdq349 Brahmkhatri, 2015, Insulin-like growth factor system in cancer: novel targeted therapies, BioMed Res Int, 2015, 538019, 10.1155/2015/538019 Evdokimova, 2012, IGFBP7 binds to the IGF-1 receptor and blocks its activation by insulin-like growth factors, Sci Signal, 5, ra92, 10.1126/scisignal.2003184 Bach, 2018, IGF-binding proteins, J Mol Endocrinol, 61, T11, 10.1530/JME-17-0254 Chitnis, 2008, The type 1 insulin-like growth factor receptor pathway, Clin Cancer Res, 14, 6364, 10.1158/1078-0432.CCR-07-4879 Baxter, 2014, IGF binding proteins in cancer: mechanistic and clinical insights, Nat Rev Cancer, 14, 329, 10.1038/nrc3720 Pollak, 2012, The insulin and insulin-like growth factor receptor family in neoplasia: an update, Nat Rev Cancer, 12, 159, 10.1038/nrc3215 Tognon, 2012, Targeting the insulin-like growth factor 1 receptor (IGF1R) signaling pathway for cancer therapy, Expert Opin Ther Targets, 16, 33, 10.1517/14728222.2011.638626 Adams, 2000, Structure and function of the type 1 insulin-like growth factor receptor, Cell Mol Life Sci, 57, 1050, 10.1007/PL00000744 Arcaro, 2013, Targeting the insulin-like growth factor-1 receptor in human cancer, Front Pharmacol, 4, 30, 10.3389/fphar.2013.00030 Mancarella, 2021, Novel regulators of the IGF system in cancer, Biomolecules, 11, 273, 10.3390/biom11020273 Pandini, 2002, Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved, J Biol Chem, 277, 39684, 10.1074/jbc.M202766200 Rozengurt, 2010, Crosstalk between insulin/insulin-like growth factor-1 receptors and G protein-coupled receptor signaling systems: a novel target for the antidiabetic drug metformin in pancreatic cancer, Clin Cancer Res, 16, 2505, 10.1158/1078-0432.CCR-09-2229 Sanabria-Figueroa, 2015, Insulin-like growth factor-1 receptor signaling increases the invasive potential of human epidermal growth factor receptor 2-overexpressing breast cancer cells via Src-focal adhesion kinase and forkhead box protein M1, Mol Pharmacol, 87, 150, 10.1124/mol.114.095380 Cevenini, 2018, Molecular signatures of the insulin-like growth factor 1-mediated epithelial-mesenchymal transition in breast, lung and gastric cancers, Int J Mol Sci, 19, E2411, 10.3390/ijms19082411 Aleksic, 2017, IGF-1R associates with adverse outcomes after radical radiotherapy for prostate cancer, Br J Cancer, 117, 1600, 10.1038/bjc.2017.337 Dale, 2015, IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer, Carcinogenesis, 36, 648, 10.1093/carcin/bgv053 Farabaugh, 2015, Role of IGF1R in breast cancer subtypes, stemness, and lineage differentiation, Front Endocrinol, 6, 59, 10.3389/fendo.2015.00059 Solomon-Zemler, 2017, Nuclear insulin-like growth factor-1 receptor (IGF1R) displays proliferative and regulatory activities in non-malignant cells, PLoS One, 12, e0185164, 10.1371/journal.pone.0185164 Alkhayyal, 2020, Correlation of insulin-like growth factor 1 receptor expression with different molecular subtypes of breast cancer in the UAE, Anticancer Res, 40, 1555, 10.21873/anticanres.14102 Ekyalongo, 2017, Revisiting the IGF-1R as a breast cancer target, NPJ Precis Oncol, 1, 14, 10.1038/s41698-017-0017-y Nahta, 2005, Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells, Cancer Res, 65, 11118, 10.1158/0008-5472.CAN-04-3841 Kang, 2014, Association of polymorphisms and haplotypes in the insulin-like growth factor 1 receptor (IGF1R) gene with the risk of breast cancer in Korean women, PLoS One, 9, e84532, 10.1371/journal.pone.0084532 Stanilov, 2014, Association of insulin-like growth factor-I receptor polymorphism with colorectal cancer development, Mol Biol Rep, 41, 8099, 10.1007/s11033-014-3708-2 Dong, 2010, Insulin-like growth factor axis gene polymorphisms and clinical outcomes in pancreatic cancer, Gastroenterology, 139, 464, 10.1053/j.gastro.2010.04.042 Yuan, 2020, A possible link of genetic variations in ER/IGF1R pathway and risk of melanoma, Int J Mol Sci, 21, E1776, 10.3390/ijms21051776 Powell, 2019, Pregnancy hypertension and a commonly inherited IGF1R variant (rs2016347) reduce breast cancer risk by enhancing mammary gland involution, JAMA Oncol, 2019, 6018432 Sarfstein, 2012, Insulin-like growth factor-I receptor (IGF-IR) translocates to nucleus and autoregulates IGF-IR gene expression in breast cancer cells, J Biol Chem, 287, 2766, 10.1074/jbc.M111.281782 Yuen, 2007, The VHL tumor suppressor inhibits expression of the IGF1R and its loss induces IGF1R upregulation in human clear cell renal carcinoma, Oncogene, 26, 6499, 10.1038/sj.onc.1210474 Werner, 2012, Tumor suppressors govern insulin-like growth factor signaling pathways: implications in metabolism and cancer, Oncogene, 31, 2703, 10.1038/onc.2011.447 Schayek, 2010, Transcription factor E2F1 is a potent transactivator of the insulin-like growth factor-I receptor (IGF-IR) gene, Growth Hormone IGF Res, 20, 68, 10.1016/j.ghir.2009.08.001 Sun, 2018, Up-regulation of INSR/IGF1R by C-myc promotes TSCC tumorigenesis and metastasis through the NF-κB pathway, Biochim Biophys Acta BBA Mol Basis Dis, 1864, 1873, 10.1016/j.bbadis.2018.03.004 Werner, 2018, Oncogenic fusion proteins adopt the insulin-like growth factor signaling pathway, Mol Cancer, 17, 28, 10.1186/s12943-018-0807-z Idelman, 2003, WT1-p53 interactions in insulin-like growth factor-I receptor gene regulation, J Biol Chem, 278, 3474, 10.1074/jbc.M211606200 Abramovitch, 2003, BRCA1-Sp1 interactions in transcriptional regulation of the IGF-IR gene, FEBS Lett, 541, 149, 10.1016/S0014-5793(03)00315-6 Riedemann, 2007, The EGF receptor interacts with the type 1 IGF receptor and regulates its stability, Biochem Biophys Res Commun, 355, 707, 10.1016/j.bbrc.2007.02.012 Lukanova, 2002, Circulating levels of insulin-like growth factor-I and risk of ovarian cancer, Int J Cancer, 101, 549, 10.1002/ijc.10613 Roddam, 2008, Insulin-like growth factors, their binding proteins, and prostate cancer risk: analysis of individual patient data from 12 prospective studies, Ann Intern Med, 149, 461, 10.7326/0003-4819-149-7-200810070-00006 Qian, 2020, Circulating insulin-like growth factor-1 and risk of total and 19 site-specific cancers: cohort study analyses from the UK biobank, Cancer Epidemiol Biomarkers Prev, 29, 2332, 10.1158/1055-9965.EPI-20-0743 Unger, 2017, Stromal-derived IGF2 promotes colon cancer progression via paracrine and autocrine mechanisms, Oncogene, 36, 5341, 10.1038/onc.2017.116 Bianconi, 2016, Integrins in the spotlight of cancer, Int J Mol Sci, 17, E2037, 10.3390/ijms17122037 Takada, 2017, Crosstalk between insulin-like growth factor (IGF) receptor and integrins through direct integrin binding to IGF1, Cytokine Growth Factor Rev, 34, 67, 10.1016/j.cytogfr.2017.01.003 Fujita, 2012, Cross-talk between integrin alpha6beta4 and insulin-like growth factor-1 receptor (IGF1R) through direct alpha6beta4 binding to IGF1 and subsequent alpha6beta4-IGF1-IGF1R ternary complex formation in anchorage-independent conditions, J Biol Chem, 287, 12491, 10.1074/jbc.M111.304170 Cedano Prieto, 2017, Direct integrin binding to insulin-like growth factor-2 through the C-domain is required for insulin-like growth factor receptor type 1 (IGF1R) signaling, PLoS One, 12, e0184285, 10.1371/journal.pone.0184285 Lin, 2012, An activity-based probe reveals dynamic protein-protein interactions mediating IGF-1R transactivation by the GABA(B) receptor, Biochem J, 443, 627, 10.1042/BJ20120188 Arang, 2020, G Protein-Coupled receptors and heterotrimeric G proteins as cancer drivers, FEBS Lett, 594, 4201, 10.1002/1873-3468.14017 Hallak, 2000, Association of heterotrimeric G(i) with the insulin-like growth factor-I receptor. Release of G(betagamma) subunits upon receptor activation, J Biol Chem, 275, 2255, 10.1074/jbc.275.4.2255 Dalle, 2001, Insulin and insulin-like growth factor I receptors utilize different G protein signaling components, J Biol Chem, 276, 15688, 10.1074/jbc.M010884200 Luttrell, 1995, G beta gamma subunits mediate mitogen-activated protein kinase activation by the tyrosine kinase insulin-like growth factor 1 receptor, J Biol Chem, 270, 16495, 10.1074/jbc.270.28.16495 Schillaci, 2006, Immunization with murine breast cancer cells treated with antisense oligodeoxynucleotides to type I insulin-like growth factor receptor induced an antitumoral effect mediated by a CD8+ response involving Fas/Fas ligand cytotoxic pathway, J Immunol, 176, 3426, 10.4049/jimmunol.176.6.3426 Morin-Brureau, 2015, Enhancement of glioma-specific immunity in mice by “NOBEL”, an insulin-like growth factor 1 receptor antisense oligodeoxynucleotide, Cancer Immunol Immunother, 64, 447, 10.1007/s00262-015-1654-z Durfort, 2012, Small interfering RNA targeted to IGF-IR delays tumor growth and induces proinflammatory cytokines in a mouse breast cancer model, PLoS One, 7, e29213, 10.1371/journal.pone.0029213 Andrews, 2001, Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas, J Clin Oncol, 19, 2189, 10.1200/JCO.2001.19.8.2189 Andrews, 2021, Phase Ib clinical trial of IGV-001 for patients with newly diagnosed glioblastoma, Clin Cancer Res, 27, 1912, 10.1158/1078-0432.CCR-20-3805 Harshyne, 2015, Glioblastoma exosomes and IGF-1R/AS-ODN are immunogenic stimuli in a translational research immunotherapy paradigm, Cancer Immunol Immunother, 64, 299, 10.1007/s00262-014-1622-z Yuen, 2009, Validation of the type 1 insulin-like growth factor receptor as a therapeutic target in renal cancer, Mol Cancer Therapeut, 8, 1448, 10.1158/1535-7163.MCT-09-0101 Khodaei, 2021, DDAB cationic lipid-mPEG, PCL copolymer hybrid nano-carrier synthesis and application for delivery of siRNA targeting IGF-1R into breast cancer cells, Clin Transl Oncol, 23, 1167, 10.1007/s12094-020-02507-3 Gualberto, 2009, Emerging role of insulin-like growth factor receptor inhibitors in oncology: early clinical trial results and future directions, Oncogene, 28, 3009, 10.1038/onc.2009.172 Olmos, 2010, Biological rationale and current clinical experience with anti-insulin-like growth factor 1 receptor monoclonal antibodies in treating sarcoma: twenty years from the bench to the bedside, Cancer J, 16, 183, 10.1097/PPO.0b013e3181dbebf9 Wang, 2014, Anti-IGF-1R monoclonal antibody inhibits the carcinogenicity activity of acquired trastuzumab-resistant SKOV3, J Ovarian Res, 7, 103, 10.1186/s13048-014-0103-5 Broussas, 2009, Molecular mechanisms involved in activity of h7C10, a humanized monoclonal antibody, to IGF-1 receptor, Int J Cancer, 124, 2281, 10.1002/ijc.24186 Calzone, 2013, Epitope-specific mechanisms of IGF1R inhibition by ganitumab, PLoS One, 8, e55135, 10.1371/journal.pone.0055135 Fuchs, 2015, A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial, Ann Oncol, 26, 921, 10.1093/annonc/mdv027 Langer, 2014, Randomized, phase III trial of first-line figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone in patients with advanced non-small-cell lung cancer, J Clin Oncol, 32, 2059, 10.1200/JCO.2013.54.4932 Sclafani, 2015, A randomized phase II/III study of dalotuzumab in combination with cetuximab and irinotecan in chemorefractory, KRAS wild-type, metastatic colorectal cancer, J Natl Cancer Inst, 107, djv258, 10.1093/jnci/djv258 Zheng, 2012, Β-Arrestin-biased agonism as the central mechanism of action for insulin-like growth factor 1 receptor-targeting antibodies in Ewing's sarcoma, Proc Natl Acad Sci USA, 109, 20620, 10.1073/pnas.1216348110 Cohen, 2005, Combination therapy enhances the inhibition of tumor growth with the fully human anti-type 1 insulin-like growth factor receptor monoclonal antibody CP-751, 871, Clin Cancer Res, 11, 2063, 10.1158/1078-0432.CCR-04-1070 Chughtai, 2020, The nuclear translocation of insulin-like growth factor receptor and its significance in cancer cell survival, Cell Biochem Funct, 38, 347, 10.1002/cbf.3479 Frappaz, 2016, Phase 1 study of dalotuzumab monotherapy and ridaforolimus-dalotuzumab combination therapy in paediatric patients with advanced solid tumours, Eur J Cancer, 62, 9, 10.1016/j.ejca.2016.03.084 Huang, 2011, R1507, an anti-insulin-like growth factor-1 receptor (IGF-1R) antibody, and EWS/FLI-1 siRNA in Ewing’s sarcoma: convergence at the IGF/IGFR/Akt axis, PLoS One, 6, e26060, 10.1371/journal.pone.0026060 Vlahovic, 2018, A phase I trial of the IGF-1R antibody ganitumab (AMG 479) in combination with everolimus (RAD001) and panitumumab in patients with advanced cancer, Oncol, 23, 782, 10.1634/theoncologist.2016-0377 Tap, 2012, Phase II study of ganitumab, a fully human anti-type-1 insulin-like growth factor receptor antibody, in patients with metastatic Ewing family tumors or desmoplastic small round cell tumors, J Clin Oncol, 30, 1849, 10.1200/JCO.2011.37.2359 Tolcher, 2009, Phase I, pharmacokinetic, and pharmacodynamic study of AMG 479, a fully human monoclonal antibody to insulin-like growth factor receptor 1, J Clin Oncol, 27, 5800, 10.1200/JCO.2009.23.6745 Kindler, 2012, A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer, Ann Oncol, 23, 2834, 10.1093/annonc/mds142 McCaffery, 2013, Putative predictive biomarkers of survival in patients with metastatic pancreatic adenocarcinoma treated with gemcitabine and ganitumab, an IGF1R inhibitor, Clin Cancer Res, 19, 4282, 10.1158/1078-0432.CCR-12-1840 Cen, 2007, Phosphorylation profiles of protein kinases in alveolar and embryonal rhabdomyosarcoma, Mod Pathol, 20, 936, 10.1038/modpathol.3800834 Abraham, 2012, An adaptive Src-PDGFRA-Raf axis in rhabdomyosarcoma, Biochem Biophys Res Commun, 426, 363, 10.1016/j.bbrc.2012.08.092 Kundranda, 2020, Randomized, double-blind, placebo-controlled phase II study of istiratumab (MM-141) plus nab-paclitaxel and gemcitabine versus nab-paclitaxel and gemcitabine in front-line metastatic pancreatic cancer (CARRIE), Ann Oncol, 31, 79, 10.1016/j.annonc.2019.09.004 Camblin, 2018, Dual inhibition of IGF-1R and ErbB3 enhances the activity of gemcitabine and nab-paclitaxel in preclinical models of pancreatic cancer, Clin Cancer Res, 24, 2873, 10.1158/1078-0432.CCR-17-2262 Camblin, 2019, Dual targeting of IGF-1R and ErbB3 as a potential therapeutic regimen for ovarian cancer, Sci Rep, 9, 16832, 10.1038/s41598-019-53322-y de Bono, 2020, Two first-in-human studies of xentuzumab, a humanised insulin-like growth factor (IGF)-neutralising antibody, in patients with advanced solid tumours, Br J Cancer, 122, 1324, 10.1038/s41416-020-0774-1 Friedbichler, 2014, Pharmacodynamic and antineoplastic activity of BI 836845, a fully human IGF ligand-neutralizing antibody, and mechanistic rationale for combination with rapamycin, Mol Cancer Therapeut, 13, 399, 10.1158/1535-7163.MCT-13-0598 Cao, 2020, Blockade of IGF/IGF-1R signaling axis with soluble IGF-1R mutants suppresses the cell proliferation and tumor growth of human osteosarcoma, Am J Cancer Res, 10, 3248 Zhang, 2021, IGF-1R anti-idiotypic antibody antagonist exhibited anti-ovarian cancer bioactivity and reduced cisplatin resistance, Hum Cell, 34, 1197, 10.1007/s13577-021-00535-x King, 2014, Can we unlock the potential of IGF-1R inhibition in cancer therapy?, Cancer Treat Rev, 40, 1096, 10.1016/j.ctrv.2014.07.004 Carboni, 2009, BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R/IR, Mol Cancer Therapeut, 8, 3341, 10.1158/1535-7163.MCT-09-0499 Kuhn, 2012, Targeting the insulin-like growth factor-1 receptor to overcome bortezomib resistance in preclinical models of multiple myeloma, Blood, 120, 3260, 10.1182/blood-2011-10-386789 Khan, 2021, A phase-1 trial of linsitinib (OSI-906) in combination with bortezomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma, Leuk Lymphoma, 62, 1721, 10.1080/10428194.2021.1876864 Ekman, 2016, A novel oral insulin-like growth factor-1 receptor pathway modulator and its implications for patients with non-small cell lung carcinoma: a phase I clinical trial, Acta Oncol, 55, 140, 10.3109/0284186X.2015.1049290 Aiken, 2017, Phase I clinical trial of AXL1717 for treatment of relapsed malignant astrocytomas: analysis of dose and response, Oncotarget, 8, 81501, 10.18632/oncotarget.20662 Scopim-Ribeiro, 2021, NT157, an IGF1R-IRS1/2 inhibitor, exhibits antineoplastic effects in pre-clinical models of chronic myeloid leukemia, Invest N Drugs, 39, 736, 10.1007/s10637-020-01028-8 Chalouni, 2018, Fate of antibody-drug conjugates in cancer cells, J Exp Clin Cancer Res, 37, 20, 10.1186/s13046-017-0667-1 Hafeez, 2020, Antibody-drug conjugates for cancer therapy, Molecules, 25, E4764, 10.3390/molecules25204764 Akla, 2020, Efficacy of the antibody-drug conjugate W0101 in preclinical models of IGF-1 receptor overexpressing solid tumors, Mol Cancer Therapeut, 19, 168, 10.1158/1535-7163.MCT-19-0219 Venepalli, 2019, Phase I study of IGF-methotrexate conjugate in the treatment of advanced tumors expressing IGF-1R, Am J Clin Oncol, 42, 862, 10.1097/COC.0000000000000611 McTavish, 2009, Novel insulin-like growth factor-methotrexate covalent conjugate inhibits tumor growth in vivo at lower dosage than methotrexate alone, Transl Res, 153, 275, 10.1016/j.trsl.2009.02.005 Alkhateeb, 2020, Phase 1b study of IGF-methotrexate conjugate in the treatment of high-grade myelodysplastic syndromes, Anticancer Res, 40, 3883, 10.21873/anticanres.14378 Solomon, 2020, Development and preclinical evaluation of cixutumumab drug conjugates in a model of insulin growth factor receptor I (IGF-1R) positive cancer, Sci Rep, 10, 18549, 10.1038/s41598-020-75279-z Hua, 2020, Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy, J Hematol Oncol, 13, 64, 10.1186/s13045-020-00904-3 Chitnis, 2014, IGF-1R inhibition enhances radiosensitivity and delays double-strand break repair by both non-homologous end-joining and homologous recombination, Oncogene, 33, 5262, 10.1038/onc.2013.460 Ramcharan, 2015, IGF-1R inhibition induces schedule-dependent sensitization of human melanoma to temozolomide, Oncotarget, 6, 39877, 10.18632/oncotarget.5631 Singh, 2014, IGF-1R inhibition potentiates cytotoxic effects of chemotherapeutic agents in early stages of chemoresistant ovarian cancer cells, Cancer Lett, 354, 254, 10.1016/j.canlet.2014.08.023 Aleksic, 2010, Type 1 insulin-like growth factor receptor translocates to the nucleus of human tumor cells, Cancer Res, 70, 6412, 10.1158/0008-5472.CAN-10-0052 Warsito, 2012, Nuclear IGF1R is a transcriptional co-activator of LEF1/TCF, EMBO Rep, 13, 244, 10.1038/embor.2011.251 Jones, 2004, Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells, Endocr Relat Cancer, 11, 793, 10.1677/erc.1.00799 Wang, 2020, Transient IGF-1R inhibition combined with osimertinib eradicates AXL-low expressing EGFR mutated lung cancer, Nat Commun, 11, 4607, 10.1038/s41467-020-18442-4 MacAulay, 2016, Phase I dose-escalation study of Linsitinib (OSI-906) and Erlotinib in patients with advanced solid tumors, Clin Cancer Res, 22, 2897, 10.1158/1078-0432.CCR-15-2218 Leighl, 2017, Phase 2 study of Erlotinib in combination with Linsitinib (OSI-906) or placebo in chemotherapy-naive patients with non-small-cell lung cancer and activating epidermal growth factor receptor mutations, Clin Lung Cancer, 18, 34, 10.1016/j.cllc.2016.07.007 Luo, 2021, Disruption of FOXO3a-miRNA feedback inhibition of IGF2/IGF-1R/IRS1 signaling confers Herceptin resistance in HER2-positive breast cancer, Nat Commun, 12, 2699, 10.1038/s41467-021-23052-9 Browne, 2012, Evaluation of IGF1R and phosphorylated IGF1R as targets in HER2-positive breast cancer cell lines and tumours, Breast Cancer Res Treat, 136, 717, 10.1007/s10549-012-2260-9 Zhang, 2018, IGF1R signaling drives antiestrogen resistance through PAK2/PIX activation in luminal breast cancer, Oncogene, 37, 1869, 10.1038/s41388-017-0027-9 Ye, 2003, Combined effects of tamoxifen and a chimeric humanized single chain antibody against the type I IGF receptor on breast tumor growth in vivo, Horm Metab Res, 35, 836 Chakraborty, 2010, Co-targeting the insulin-like growth factor I receptor enhances growth-inhibitory and pro-apoptotic effects of anti-estrogens in human breast cancer cell lines, Breast Cancer Res Treat, 120, 327, 10.1007/s10549-009-0382-5 McDermott, 2017, Dual inhibition of IGF1R and ER enhances response to trastuzumab in HER2 positive breast cancer cells, Int J Oncol, 50, 2221, 10.3892/ijo.2017.3976 Flanigan, 2013, Overcoming IGF1R/IR resistance through inhibition of MEK signaling in colorectal cancer models, Clin Cancer Res, 19, 6219, 10.1158/1078-0432.CCR-13-0145 Cao, 2015, Combinational therapy enhances the effects of anti-IGF-1R mAb figitumumab to target small cell lung cancer, PLoS One, 10, e0135844, 10.1371/journal.pone.0135844 Xue, 2021, Metformin and an insulin/IGF-1 receptor inhibitor are synergistic in blocking growth of triple-negative breast cancer, Breast Cancer Res Treat, 185, 73, 10.1007/s10549-020-05927-5 Fuentes-Baile, 2020, Differential effects of IGF-1R small molecule tyrosine kinase inhibitors BMS-754807 and OSI-906 on human cancer cell lines, Cancers, 12, E3717, 10.3390/cancers12123717 Lee, 2015, STAT3-mediated IGF-2 secretion in the tumour microenvironment elicits innate resistance to anti-IGF-1R antibody, Nat Commun, 6, 8499, 10.1038/ncomms9499 Bano, 2020, Analyzing structural differences between insulin receptor (IR) and IGF1R for designing small molecule allosteric inhibitors of IGF1R as novel anti-cancer agents, Growth Hormone IGF Res, 55, 101343, 10.1016/j.ghir.2020.101343 Codony-Servat, 2017, Nuclear IGF-1R predicts chemotherapy and targeted therapy resistance in metastatic colorectal cancer, Br J Cancer, 117, 1777, 10.1038/bjc.2017.279 Aleksic, 2018, Nuclear IGF1R interacts with regulatory regions of chromatin to promote RNA polymerase II recruitment and gene expression associated with advanced tumor stage, Cancer Res, 78, 3497, 10.1158/0008-5472.CAN-17-3498 Sehat, 2010, SUMOylation mediates the nuclear translocation and signaling of the IGF-1 receptor, Sci Signal, 3, ra10, 10.1126/scisignal.2000628 Deng, 2011, Over-accumulation of nuclear IGF-1 receptor in tumor cells requires elevated expression of the receptor and the SUMO-conjugating enzyme Ubc9, Biochem Biophys Res Commun, 404, 667, 10.1016/j.bbrc.2010.12.038